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Background: Severe duodeno-gastro-oesophageal reflux (ODOR) is a risk factor for oesophagitis and Barrett's oesophagus. Patients with non-erosive reflux disease (NERD) have a slight increase in DOOR. Patients with gastro-oesophageal reflux disease (GORD), who are taking proton pump inhibitors (PPIs), still have reflux but of weakly acidic pH and persistence of bile. In these two groups of patients, heartburn might be due to increased oesophageal mucosal permeability and dilated intercellular spaces (DIS). We aimed to assess whether experimental short exposure of the oesophageal mucosa to bile acids, in low concentrations (at acidic, weakly acidic and neutral conditions) can increase mucosal permeability and provoke DIS. Methods: Rabbit oesophageal mucosa was studied in diffusion and Ussing chambers. We assessed the effects of different solutions containing bile acids, applied to the mucosal side, on transepithelial electrical resistance (RT) and permeability to fluorescein. The diameter of intercellular spaces was assessed by using transmission electron microscopy. Results: Incubation of oesophageal mucosa with acidic solutions (pH 2.0) containing a range of bile acids (0.5-5 mmol/l) markedly decreased RT and increased mucosal permeability. Weakly acidic solutions (pH 5.0), and to some extent neutral solutions (pH 7.4), containing some bile acids also decreased RT and increased permeability, although the effects were much less marked and in some combinations no effect was seen. Exposure to bile acids provoked DIS in acid and weakly acidic conditions but not in neutral (pH 7.4) solutions. Conclusions: Experimental short exposure of the oesophageal mucosa to solutions with a bile acid concentration and acidity similar to that observed in the gastric contents of patients with NERD or ERD, and who are taking PPIs, may impair oesophageal mucosal integrity and even induce dilated intercellular spaces. Such a situation could, theoretically, underlie the occurrence and! or persistence of symptoms in these patients. [ABSTRACT FROM AUTHOR]

Cavoportal hemitransposition (CPHT) is a rarely performed treatment technique in liver transplantation in cases of extensive splanchnic thrombosis, in which the inferior vena cava of the recipient is used to perfuse the portal vein of the allograft. A case of a 65-year-old liver transplantation patient with an acutely thrombosed cavoportal anastomosis is presented. After unsuccessful medical treatment, recanalization was obtained with transfemoral catheter directed thrombolysis, angioplasty and stent placement. Although this type of treatment has been extensively documented for the management of portal anastomotic problems after orthotopic liver transplantation, data on its application in modified transplantation techniques including CPHT are rare. This technique provides a minimally invasive treatment option in CPHT patients with cavoportal anastomotic problems, who might otherwise require complex surgical repair or retransplantation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

1:  The European Society of Gastrointestinal Endoscopy (ESGE) adheres to the overarching principles of equality of opportunity, fair treatment, nondiscrimination, and diversity of health care professionals. 2:  ESGE strongly supports the creation of collaborations within and between national and international endoscopy societies to disseminate the principles of diversity, equality, and inclusion (DEI) in the field of gastrointestinal (GI) endoscopy. 3:  ESGE aims to reflect the diversity of its membership in all its scientific and educational activities. 4:  ESGE supports the fostering of collaborative work settings that empower all members of the endoscopy team to reach their full potential. 5:  ESGE supports international and national endoscopy societies in promoting equitable access to high quality endoscopy training. 6:  ESGE recommends the implementation of ergonomic principles in endoscopy units to prevent injuries and to provide adapted workplace conditions for personnel with disabilities and/or special needs. 7:  ESGE recommends comprehensive mentorship, that includes diverse backgrounds, and equitable sponsorship for professional development, training, and academic excellence. 8:  ESGE recommends that endoscopists actively identify, discuss, and attempt to accommodate reasonable patient preferences and expectations regarding endoscopy procedures. 9:  ESGE advocates for educational and awareness campaigns targeting both health care professionals and patients, as well as the adoption of cost-effective health care strategies to address disparities and enhance equity in endoscopy care. 10:  ESGE is committed to increasing support for underrepresented scholars and minorities pursuing research in endoscopy. 11:  ESGE identifies mentorship and sponsorship as factors that may mitigate the barriers to academic careers for underrepresented endoscopy scholars. 12:  ESGE recognizes the need to increase awareness of diversity, equity, and inclusion (DEI) in the field of endoscopy and supports publications on these topics., Competing Interests: No competing interests have been declared by any author., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Background and Aims: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and nonrecovery in ACLF., Approach and Results: Here, we mapped the single-cell transcriptome of circulating immune cells from patients with ACLF and acute decompensated (AD) cirrhosis and healthy individuals. We further interrogate how these findings, as well as immunometabolic and functional profiles, associate with ACLF-recovery (ACLF-R) or nonrecovery (ACLF-NR). Our analysis unveiled 2 distinct states of classical monocytes (cMons). Hereto, ACLF-R cMons were characterized by transcripts associated with immune and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1 . Additional metabolomic and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program, and blunted activation among lymphoid populations in patients with ACLF-R. Conversely, ACLF-NR cMon featured elevated expression of inflammatory and stress response genes such as VIM , LGALS2 , and TREM1 , along with blunted metabolic activity and increased functionality., Conclusions: This study identifies distinct immunometabolic cellular states that contribute to disease outcomes in patients with ACLF. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or nonrecovery phenotypes, which may be harnessed as potential therapeutic targets in the future., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) with lumen apposing metal stent is emerging both as a rescue strategy and a primary treatment for distal malignant biliary obstruction. The large-scale diffusion of the procedure and improved overall survival of patients with pancreatobiliary neoplasms is resulting in a growing population of long-term EUS-CDS lumen apposing metal stent carriers. Recent studies have reported a need for reintervention during follow-up as high as 55%, and the Leuven-Amsterdam-Milan Study Group classification has been developed, identifying five mechanisms of stent dysfunction and 11 possible rescue strategies aimed at restoring biliary drainage. This illustrated technical review aims to further dissect the recent classification through a comprehensive analysis of nine illustrative cases, offering insights into the pathophysiology underlying dysfunction and clinical reasoning behind rescue interventions, as well as technical considerations and practical tips and tricks. By exploring mechanisms of dysfunction, this review also assists clinicians in selecting the ideal candidates for EUS-CDS while identifying patients deemed high risk for dysfunction or clinical failure., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

De novo malignancy (DNM) is the primary cause of mortality after liver transplantation (LT) for alcohol-related liver disease (ALD). However, data on risk factors for DNM development after LT are limited, specifically in patients with ALD. Therefore, we retrospectively analyzed all patients transplanted for ALD at our center before October 2016. Patients with a post-LT follow-up of <12 months, DNM within 12 months after LT, patients not on tacrolimus in the 1st year post-LT, and unknown smoking habits were excluded. Tacrolimus drug exposure level (TDEL) was calculated by area under the curve of trough levels in the 1st year post-LT. 174 patients received tacrolimus of which 19 (10.9%) patients developed a DNM between 12 and 60 months post-LT. Multivariate cox regression analysis identified TDEL [HR: 1.710 (1.211-2.414); p = 0.002], age [1.158 (1.076-1.246); p < 0.001], number of pack years pre-LT [HR: 1.021 (1.004-1.038); p = 0.014] and active smoking at LT [HR: 3.056 (1.072-8.715); p = 0.037] as independent risk factors for DNM. Tacrolimus dose minimization in the 1st year after LT and smoking cessation before LT might lower DNM risk in patients transplanted for ALD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Vanlerberghe, van Malenstein, Sainz-Barriga, Jochmans, Cassiman, Monbaliu, van der Merwe, Pirenne, Nevens and Verbeek.)

Background & Aims: Concomitant respiratory disease is a common finding in patients with hepatopulmonary syndrome (HPS). Among patients who underwent liver transplantation (LT) for HPS, we compared characteristics and outcome of patients with versus without concomitant respiratory disease., Methods: This single center retrospective observational study included patients with HPS who underwent LT between 1999 and 2020., Results: During the study period, 32 patients with HPS received a LT; nine (28%) with concomitant respiratory disease of whom one required a combined lung-liver transplantation. Patients with concomitant respiratory disease had higher PaCO2 (38 vs. 33 mm Hg, p = .031). The 30-day postoperative mortality was comparable, but the estimated cumulative probability of resolution of oxygen therapy after LT in HPS patients with versus those without concomitant respiratory disease was lower: 63% versus 91% at 12 months and 63% versus 100% at 18 months (HR 95% CI .140-.995, p = .040). In addition to the presence of concomitant respiratory disease (p = .040), history of smoking (p = .012), and high baseline 99mTcMAA shunt fraction (≥20%) (p = .050) were significantly associated with persistent need of oxygen therapy. The 5-year estimated cumulative probability of mortality in patients with concomitant respiratory disease was worse: 50% versus 23% (HR 95% CI .416-6.867, p = .463)., Conclusions: The presence of a concomitant respiratory disease did not increase the short-term postoperative mortality after LT in patients with HPS. However, it resulted in a longer need for oxygen therapy., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Objectives: EUS-guided pancreatic duct drainage (EUS-PD) using rendez-vous has been suggested as a safer alternative to pancreatogastrostomy. Fibrostenotic disease in the pancreatic head may however preclude major papilla rendez-vous, leading to preferential guidewire advancement through the minor papilla. Our aim was to compare the outcomes of minor and major papilla rendez-vous., Methods: This is a tertiary single-center retrospective analysis of all consecutive EUS-PD procedures performed from 2015 to April 2022. EUS-PD was only performed following failed retrograde attempts. Successful EUS-PD rendez-vous cases were included and minor and major papilla procedures were compared., Results: Thirty-three patients were included in the final analysis (66.6% male, mean age 56.1 [SD±14.8] years, 54.6% active smokers). In 21 patients (63.6%), minor papilla rendez-vous was attained. Clinical success was achieved in 81.0% vs. 58.3% in the major papilla group (p = 0.230). The overall incidence of AE was similar in both groups (9 [42.9%] vs. 4 [33.3%] events, p = 0.719), with a comparable distribution in severe, moderate and mild AE. Incidence of recurrent pancreatitis was almost identical (28.6% vs. 25.0%, p = 1.000)., Conclusions: For patients with symptomatic chronic pancreatitis, EUS-PD using minor or major papilla rendez-vous attained similar results, suggesting that pancreatic duct drainage through the minor papilla can be considered as equally effective., Competing Interests: Conflict of interest Michiel Bronswijk and Diederik Persyn declare no competing interests. Schalk van der Merwe holds the Cook chair in Interventional endoscopy and holds consultancy agreements with Cook, Pentax and Olympus. Wim Laleman co-chairs the Boston-Scientific Chair in Therapeutic Biliopancreatic Endoscopy with Schalk Van der Merwe and has consultancy agreements with Boston Scientific and Cook. Hannah van Malenstein holds a consultancy agreement with Boston-Scientific., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Polycystic liver disease (PLD) can lead to extensive hepatomegaly. Symptom relief is the primary goal of the treatment. The role of the recently developed disease-specific questionnaires for identification of the thresholds and the assessment of therapy needs further investigation., Methods: A five-year prospective multi-centric observational study in 21 hospitals in Belgium gathered a study population of 198 symptomatic PLD-patients of whom the disease-specific symptom questionnaire PLD-complaint-specific assessment (POLCA) scores were calculated. The thresholds of the POLCA score for the need for volume reduction therapy were analyzed., Results: The study group consisted of mostly (82.8%) women with baseline mean age of 54.4 years ±11.2, median liver volume expressed as height-adjusted total liver volume(htLV) of 1994 mL (interquartile range [IQR] 1275; 3150) and median growth of the liver of +74 mL/year (IQR +3; +230). Volume reduction therapy was needed in 71 patients (35.9%). A POLCA severity score (SPI) ≥ 14 predicted the need for therapy both in the derivation (n = 63) and the validation cohort (n = 126). The thresholds to start somatostatin analogues (n = 55) or to consider liver transplantation (n = 18) were SPI scores of ≥14 and ≥ 18 and the corresponding mean htLVs were 2902 mL (IQR 1908; 3964) and 3607 mL (IQR 2901; 4337), respectively. Somatostatin analogues treatment resulted in a decrease in the SPI score -6.0 versus + 4.5 in patients without somatostatin analogues (p < 0.01). Changes in the SPI score were significantly different between the liver transplantation group and no liver transplantation group, +4.3 ± 7.1 versus -1.6 ± 4.9, respectively, (p < 0.01)., Conclusion: A polycystic liver disease-specific questionnaire can be used as a guide on when to start a volume reduction therapy and to assess the effect of treatment., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background and Aims: Gastric outlet and biliary obstruction are common manifestations of GI malignancies and some benign diseases for which standard treatment would be surgical gastroenterostomy and hepaticojejunostomy (ie, "double bypass"). Therapeutic EUS has allowed for the creation of an EUS-guided double bypass. However, same-session double EUS-guided bypass has only been described in small proof-of-concept series and lacks a comparison with surgical double bypass., Methods: A retrospective multicenter analysis was performed of all consecutive same-session double EUS-guided bypass procedures performed in 5 academic centers. Surgical comparators were extracted from these centers' databases from the same time interval. Efficacy, safety, hospital stay, nutrition and chemotherapy resumption, long-term patency, and survival were compared., Results: Of 154 identified patients, 53 (34.4%) received treatment with EUS and 101 (65.6%) with surgery. At baseline, patients undergoing EUS exhibited higher American Society of Anesthesiologists scores and a higher median Charlson Comorbidity Index (9.0 [interquartile range {IQR}, 7.0-10.0] vs 7.0 [IQR, 5.0-9.0], P < .001). Technical success (96.2% vs 100%, P = .117) and clinical success rates (90.6% vs 82.2%, P = .234) were similar when comparing EUS and surgery. Overall (11.3% vs 34.7%, P = .002) and severe adverse events (3.8% vs 19.8%, P = .007) occurred more frequently in the surgical group. In the EUS group, median time to oral intake (0 days [IQR, 0-1] vs 6 days [IQR, 3-7], P < .001) and hospital stay (4.0 days [IQR, 3-9] vs 13 days [IQR, 9-22], P < .001) were significantly shorter., Conclusions: Despite being used in a patient population with more comorbidities, same-session double EUS-guided bypass achieved similar technical and clinical success and was associated with fewer overall and severe adverse events when compared with surgical gastroenterostomy and hepaticojejunostomy., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Recently, the term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace non-alcoholic fatty liver disease (NAFLD). This concept enables diagnosing liver disease associated with metabolic dysfunction in patients with alcohol-related liver disease (ALD), a main indication for liver transplantation (LTx). We assessed MAFLD prevalence in ALD patients undergoing LTx and its prognostic value on post-LTx outcomes., Methods: We retrospectively analyzed all ALD patients transplanted at our center between 1990 and August 2020. MAFLD was diagnosed based on the presence or history of hepatic steatosis and a BMI > 25 or type II diabetes or ≥ 2 metabolic risk abnormalities at LTx. Overall survival and risk factors for recurrent liver and cardiovascular events were analyzed by Cox regression., Results: Of the 371 included patients transplanted for ALD, 255 (68.7%) had concomitant MAFLD at LTx. Median follow-up post-LTx was 72 months (IQR: 34.50-122). Patients with ALD-MAFLD were older at LTx (p = .001), more often male (p < .001) and more frequently had hepatocellular carcinoma (p < .001). No differences in perioperative mortality and overall survival were found. ALD-MAFLD patients had an increased risk of recurrent hepatic steatosis, irrespective of alcohol relapse, but no superimposed risk of cardiovascular events., Conclusions: The co-presence of MAFLD at LTx for ALD is associated with a distinct patient profile and is an independent risk factor for recurrent hepatic steatosis. The use of MAFLD criteria in ALD patients might increase awareness and treatment of specific hepatic and systemic metabolic abnormalities before and after LTx., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Objectives: Long-term outcomes of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) performed with lumen apposing metal stents (LAMS) have been poorly evaluated in small or retrospective series, leading to an underestimation of LAMS dysfunction., Methods: All consecutive EUS-CDS performed in three academic referral centers were included in prospectively maintained databases. Technical/clinical success, adverse events (AEs), and dysfunction during follow-up were retrospectively analyzed. Kaplan-Meier analysis was used to estimate dysfunction-free survival (DFS), with Cox proportional hazard regression to evaluate independent predictors of dysfunction., Results: Ninety-three patients were included (male 56%; mean age, 70 years [95% confidence interval (CI) 68-72]; pancreatic cancer 81%, metastatic disease 47%). In 67% of procedures, 6 mm LAMS were used. Technical and clinical success were achieved in 97.8% and 93.4% of patients, respectively, with AEs occurring in 9.7% (78% mild/moderate). Dysfunction occurred in 31.8% of patients after a mean of 166 days (95% CI 91-241), with an estimated 6 month and 12 month DFS of 75% and 52%, respectively; mean DFS of 394 (95% CI 307-482) days. Almost all dysfunctions (96%) were successfully managed by endoscopic reintervention. Duodenal invasion (hazard ratio 2.7 [95% CI 1.1-6.8]) was the only independent predictor of dysfunction., Conclusions: Endoscopic ultrasound-guided choledochoduodenostomy shows excellent initial efficacy and safety, although stent dysfunctions occurs frequently during long-term follow-up. Almost all stent dysfunctions can be managed successfully by endoscopic reinterventions. We propose a comprehensive classification of the different types of dysfunction that may be encountered and rescue procedures that may be employed under these circumstances. Duodenal invasion seems to increase the risk of developing EUS-CDS dysfunction, potentially representing a relative contraindication for this technique., (© 2022 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)